Wehave examined the effect of airway wall thickening, loss of lung recoil, and airway smooth muscle shortening on the Increase In airway resistance using a model of the human tracheobronchial tree. Tha values for airway wall thickening were determined morphometrlcally on the postmortem or surgically resected lungs of normal subjects, patients with moderate chronic obstructive pulmonary disease, and patlanta with severe asthma. Loss of recoil was simulated by deflating airways along their pressure-area curves by 1 to 3 cm H20. values of smooth muscle shortening between 20 and 40% were used In the model to generate sigmoidal-shaped" dose-response" curves. The analysis shows that moderate amounts of airway well thickening, which havelittle affect on baseline resistance, can profoundly affect the airway narrowing caused by smooth muscle shortening-especially If the well thickening Is localized In peripheral airways. The combination of a loss of recoil and airway wall thickening are more than additive In their effect on simulated airway responsIveness. Weconclude that airway wall thickening and a loss of lung recoil can partIally explain the airway hyperresponslveness observed In patients with chronic obstructive lung disease and asthma. AM REV RESPIR DIS 1992; 145: 1251-1258